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NEUROPHARMACOLOGY

Effect of Morphine on Deep Dorsal Horn Projection Neurons Depends on Spinal GABAergic and Glycinergic Tone: Implications for Reduced Opioid Effect in Neuropathic Pain

Department of Anesthesiology (Y.-P.C., S.-R.C., H.-L.P.) and Department of Neural and Behavioral Sciences (H.-L.P.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania; and Department of Anesthesiology (Y.-P.C.), The Second Xiang-Ya Hospital of South Central University, Changsha, People's Republic of China

The µ opioid agonist morphine has distinct effects on spinal dorsal horn neurons in the superficial and deep laminae. However, it is not clear if the inhibitory effect of morphine on dorsal horn projection neurons is secondary to its potentiating effect on inhibitory interneurons. In this study, we tested the hypothesis that removal of GABAergic and glycinergic inhibitory inputs attenuates the effect of morphine on dorsal horn projection neurons and the reduced spinal GABAergic tone contributes to attenuated morphine effect in neuropathic pain. Single-unit activity of deep dorsal horn projection neurons was recorded in anesthetized normal/sham controls and L₅ and L₆ spinal nerve-ligated rats. Spinal application of 10 µM morphine significantly inhibited the evoked responses of dorsal horn neurons in both normal/sham controls, and this effect was abolished by the specific µ opioid antagonist. However, the effect of morphine on dorsal horn projection neurons was significantly reduced in nerve-injured rats. Furthermore, topical application of the GABA_A receptor antagonist bicuculline (20 µM) almost abolished the effect of morphine in normal/sham control rats but did not significantly attenuate the morphine effect in nerve-injured rats. On the other hand, the glycine receptor antagonist strychnine (4 µM) significantly decreased the effect of morphine in both nerve-injured and control animals. These data suggest that the inhibitory effect of opioids on dorsal horn projection neurons depends on GABAergic and glycinergic inputs. Furthermore, reduced GABAergic tone probably contributes to diminished analgesic effect of opioids in neuropathic pain.

Address correspondence to: Dr. Hui-Lin Pan, Department of Anesthesiology, H187, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033. E-mail: hpan{at}psu.edu

This article has been cited by other articles:

				S.-R. Chen and H.-L. Pan Loss of TRPV1-Expressing Sensory Neurons Reduces Spinal {micro} Opioid Receptors But Paradoxically Potentiates Opioid Analgesia J Neurophysiol, May 1, 2006; 95(5): 3086 - 3096. [Abstract] [Full Text] [PDF]

				X.-L. Wang, H.-M. Zhang, D.-P. Li, S.-R. Chen, and H.-L. Pan Dynamic regulation of glycinergic input to spinal dorsal horn neurones by muscarinic receptor subtypes in rats J. Physiol., March 1, 2006; 571(2): 403 - 413. [Abstract] [Full Text] [PDF]